Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease

H.L. Martin, M. Santoro, S. Mustafa, G. Riedel, John Forrester, P. Teismann

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27 Citations (Scopus)

Abstract

© 2016 Wiley Periodicals, Inc. Parkinson's disease (PD) is the second most common neurodegenerative disease and results from the loss of dopaminergic neurons of the nigrostriatal pathway. The pathogenesis of PD is poorly understood, but inflammatory processes have been implicated. Indeed increases in the number of major histocompatibility complex II (MHC II) reactive cells have long been recognised in the brains of PD patients at post-mortem. However whether cells expressing MHC II play an active role in PD pathogenesis has not been delineated. This was addressed utilising a transgenic mouse null for MHC II and the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In wild-type mice MHC II levels in the ventral midbrain were upregulated 1-2 days after MPTP treatment and MHC II was localized in both astrocytes and microglia. MHC II null mice showed significant reductions in MPTP-induced dopaminergic neuron loss and a significantly reduced invasion of astrocytes and microglia in MHC II null mice receiving MPTP compared with controls. In addition, MHC II null mice failed to show increases in interferon-γ or tumour necrosis factor-α in the brain after MPTP treatment, as was found in wild-type mice. However, interleukin-1β was significantly increased in both wild-type and MHC II null mice. These data indicate that in addition to microglial cell/myeloid cell activation MHC Class II-mediated T cell activation is required for the full expression of pathology in this model of PD. GLIA 2016;64:386-395 Main Points: MHCII upregulation is necessary for dopaminergic cell death in a model of Parkinson's disease. The study supports the presence of an adaptive immune response in the pathogenesis of Parkinson's disease.
Original languageEnglish
Pages (from-to)386-395
JournalGlia
Volume64
Issue number3
Early online date29 Oct 2015
DOIs
Publication statusPublished - Mar 2016

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    Martin, H. L., Santoro, M., Mustafa, S., Riedel, G., Forrester, J., & Teismann, P. (2016). Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease. Glia, 64(3), 386-395. https://doi.org/10.1002/glia.22935